Background Drugs are chemicals which can disrupt the nerve cell functions of the brain. The present study aims to investigate the addiction related gene (OPRM1) in three types of addiction—drugs, alcohol and smoking. Pathway for the addiction was ascertained through KEGG database, and the hotspot mutations for various populations were identified from Gnomad-exomes database. In silico analyses like SIFT, Polyphen, Hope, I-mutant and mutation taster were performed to understand the amino acid substitution, protein function, stability and pathogenicity of the variants. Main body Addiction-related variants were found in exons 1, 2 and 3, while the exon 4 did not exhibit any addiction related variation. Among all the variants from this gene, rs1799971 (A118G) polymorphism was the most commonly studied variation for addiction in different populations worldwide. Population-wise allele and genotype frequencies, demographic and epidemiological studies have also been performed from different populations, and the possible association of these variants with addiction was evaluated. Conclusion Our findings suggest that OPRM1 polymorphism impact as pharmacogenetic predictor of response to naltrexone and can also address the genetic predisposition related to addiction in human beings.